NEW YORK (Reuters Health) - In more than a third of
patients with gastrointestinal stromal tumor (GIST), physicians
underestimate the risk of recurrence, often resulting in shorter
adjuvant therapy, according to a retrospective study.

"Given that there is no single risk-stratification system
for these patients, we hypothesized that there would be
underestimation of risk for borderline cases where the systems
might differ in their assessment of risk, but instead we found
systematic underestimation of risk even among patients assessed
to be at high risk no matter what risk-stratification system we
used," Anne Guerin, from the Analysis Group, Montreal, Quebec,
Canada, told Reuters Health by email.

Recurrence of GIST is common, even with complete resection,
and the National Comprehensive Cancer Network (NCCN) recommends
that patients at high risk of recurrence receive adjuvant
imatinib (Gleevec, Novartis) for at least 36 months following
resection.

Guerin and colleagues used information on 506 patients with
GIST from 109 oncologists to evaluate how well the physicians
assessed the risk of tumor recurrence, the impact of risk
underestimation on planned adjuvant therapy duration, and the
association between planned adjuvant therapy duration and
relapse-free survival in high-risk patients.

Most oncologists had been in practice for more than 10
years, mainly in private practice in urban settings, according
to the July 23 JAMA Oncology online report.

Based on Revised National Institutes of Health (NIH)
Consensus Criteria, 65.8% of the patients were at high risk of
recurrence, 8.7% were at intermediate risk, 10.5% were at low
risk, and 15.0% were at very low risk.

Compared with these risk assignments, physicians were right
most of the time (53.4%), but they underestimated the risk for
37.5% of patients and overestimated the risk for 9.1%.

Among intermediate-risk patients, only 27.3% in the
not-underestimated group had a treatment plan with no adjuvant
therapy, compared with 81.8% of patients in the underestimated
group (p=0.003).

Among high-risk patients, significantly more patients in
the not-underestimated group (65.9%) than in the underestimated
group (36.1%) had a treatment plan of three or more years of
adjuvant therapy (p=0.02). On the other hand, 11.0% of
not-underestimated patients had a treatment plan of one to three
years of adjuvant therapy, compared with 21.3% of underestimated
patients (p=0.001).

After three years of follow-up, relapse-free survival rates
for high-risk patients were lower for patients with
underestimated risk (38.8%) than for patients whose risk was not
underestimated (71.2%).

After adjusting for multiple factors, planned adjuvant
treatment duration of at least three years was associated with a
71% lower risk of recurrence compared with shorter-duration
adjuvant treatment.

"It is important to accurately assess the risk of
recurrence among patients who undergo GIST resection," Guerin
said. "Unfortunately, a significant proportion of patients in
our study had an assessment which underestimated their risk of
recurrence."

She reiterated, "It is important to give patients at high
risk of recurrence three years of adjuvant treatment. Many
patients in our study with unrecognized high risk of recurrence
were not given sufficient adjuvant treatment, and the patients
with insufficient adjuvant treatment had significantly shorter
recurrence-free survival compared with those who received at
least three years of adjuvant treatment."

"One of the strengths of this study is that we invited a
broad range of U.S. community oncologists to participate online
in this study, many of whom weren't affiliated with academic
medical centers and would typically have few opportunities to
participate in these kinds of studies," Guerin added. "As a
consequence, we were able to quickly and efficiently collect
information on a sizable number of GIST patients, despite the
rarity of this disease. We were able to get an idea of
real-world practice patterns to treat GIST patients, and we
identified opportunities to improve the quality of care that
these patients receive."

Dr. Heikki Joensuu, from the University of Helsinki,
Finland, wrote an invited commentary related to this report. He
told Reuters Health by email, "Some difference of opinion in
GIST risk estimation is expected, but the proportion of GIST
patients who had their risk underestimated -- more than a third
-- is unexpectedly high."

"At least one of the validated risk-stratification schemes
needs to be consulted to identify the GIST patients who most
likely benefit from adjuvant imatinib," Dr. Joensuu said. "The
most accurate available instruments are the Prognostic Heat
Maps, the Armed Forces Institute of Pathology (AFIP) scheme, and
the Revised National Institutes of Health Consensus Criteria."

Better education for physicians could include "attending an
educational lecture on the topic or simply reading the few key
publications," Dr. Joensuu said. "An educational website could
be useful."

"Mutation analysis of GIST is important to carry out to
identify the few mutations that confer imatinib resistance," Dr.
Joensuu added. "Most patients who have no mutation in KIT or
PDGFRA do not benefit from adjuvant imatinib."

Dr. Danielle A. Bischof, from Mount Sinai Hospital,
Toronto, Ontario, Canada, recently reviewed adherence to
guidelines for adjuvant imatinib therapy for GIST. She told
Reuters Health by email, "Clear reporting of risk of recurrence
using revised NIH consensus criteria on synoptic pathology
reports for all patients undergoing surgery for GIST would take
the guess-work out of risk stratification for oncologists. A
consensus statement with clear recommendations on risk
stratification and indications for adjuvant imatinib may also be
of benefit as well."

"There are well-defined criteria to determine recurrence
risk for GIST following surgery," Dr. Bischof concluded. "Three
years of imatinib following resection results in improved
overall and recurrence-free survival compared with one year.
Accurate risk stratification is essential to determine
appropriate candidates for adjuvant imatinib."

Novartis Pharmaceuticals sponsored the study, employed two
of the seven authors, provided consultancy fees to the Analysis
Group, and preapproved the comments Dr. Guerin provided for this
story.